Protein released from fat after exercise improves glucose

Laurie J. Goodyear, Ph.D., Department Head and Senior Investigator at the Joslin Diabetes Center and Professor of Medicine at Harvard Medical School. Picture credits: John Soares

Movement is known to improve one's health, but understanding how to become healthier on a molecular level is the question researchers at the Joslin Diabetes Center are answering.

After experiments on humans and mice, the researchers found that exercise training causes dramatic changes in fat. They also discovered that this "trained" fat releases factors into the bloodstream that can have a positive effect on your health. The study was published online on February 11, 2019 Nature metabolism,

It is well known that fat cells excrete proteins, called adipokines, and that many adipokines increase in obesity and have deleterious effects on the metabolism and health.

"Contrary to the negative effects of many adipokines, our study identified transforming growth factor beta 2 (TGF-beta 2) as an adipokine released from adipose tissue (fat) in response to physical activity, which actually improves glucose tolerance," says Laurie J. Goodyear, Ph.D., Head of the Joslin Department of Integrative Physiology and Metabolism and co-author of the study.

Activity-stimulated TGF-beta 2 not only improved glucose tolerance, but also treated obese mice with TGF beta 2-lowered blood lipid levels and many other aspects of metabolism.

"The fact that a single protein has such important and dramatic effects has been impressive," says Goodyear, professor of medicine at Harvard Medical School.

Two years ago, the international research team showed for the first time that adipose tissue has beneficial metabolic effects in response to athletic activity.

"Our hypothesis was that exercise changes fat, and as a result of this change, fat releases these beneficial proteins into the bloodstream," says Goodyear. "Prior to this discovery, we've always focused only on the positive effects of muscle."

Based on this finding, the Joslin researchers looked for the adipokines released from fat during exercise. They did a series of molecular experiments on humans and mice. They identified adipokine levels in men before and after a training cycle. They also studied training mice.

Their analysis identified TGF beta 2 as one of the proteins upregulated in humans and mice. Further investigation confirmed that the levels of this one adipokine increased in both cases in the adipose tissue as well as in the bloodstream under exercise.

To find out if the protein promotes beneficial metabolic effects, they treated the mice with TGF beta 2. The experiment showed a number of positive metabolic effects in the mice, including improved glucose tolerance and increased fatty acid uptake.

Next, they fed the mice on a high-fat diet, causing the animals to suffer from diabetes. In order to know if TGF beta 2 was actually responsible for the metabolic effects, they treated the diabetic mice with TGF beta 2. This reversed the negative metabolic effects of the high-fat diet, similar to exercise.

"Our findings are important as they are indeed the first demonstration of adipokine-induced metabolism that can have beneficial effects on the body," says Goodyear.

Another important finding was that lactic acid released during exercise is an integral part of the process. Lactate is released from the muscles during exercise and then enters the fat where it triggers the release of TGF beta 2.

"This research is revolutionizing the way we think about exercise and the many metabolic effects of exercise, and, importantly, fat actually plays an important role in how exercise works," says Goodyear.

These results suggest that TGF beta 2 may be a potential treatment for the treatment of high blood sugar and possibly a possible therapy for type 2 diabetes. Long-term studies will be needed to determine the safety of TGF-beta-2 treatment.

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